The Role of Natural Killer Cells in the Immune Response in Kidney Transplantation

Pontrelli, Paola; Rascio, Federica; Castellano, Giuseppe; Grandaliano, Giuseppe; Gesualdo, Loreto; Stallone, Giovanni

doi:10.3389/fimmu.2020.01454

Cited by 43 publications

(21 citation statements)

References 105 publications

(135 reference statements)

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“…Since HLA-C alleles are inhibitory ligands protecting cellular targets from NK cell lysis, antibody responses against C1/NK2 and C2/NK1 alleles may play an important role in NK cell function in the transplantation context. Although the presence of C1 and C2 alleles is part of algorithms used for better allocation of bone marrow donors, the role of NK cells in organ transplantation is not studied so much (35,36). However, very recent studies underlined a prominent role of NK1 versus NK2 responses for graft tolerance (32).…”

Section: Discussionmentioning

confidence: 99%

Hidden Patterns of Anti-HLA Class I Alloreactivity Revealed Through Machine Learning

et al. 2021

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Detection of alloreactive anti-HLA antibodies is a frequent and mandatory test before and after organ transplantation to determine the antigenic targets of the antibodies. Nowadays, this test involves the measurement of fluorescent signals generated through antibody–antigen reactions on multi-beads flow cytometers. In this study, in a cohort of 1,066 patients from one country, anti-HLA class I responses were analyzed on a panel of 98 different antigens. Knowing that the immune system responds typically to “shared” antigenic targets, we studied the clustering patterns of antibody responses against HLA class I antigens without any a priori hypothesis, applying two unsupervised machine learning approaches. At first, the principal component analysis (PCA) projections of intra-locus specific responses showed that anti-HLA-A and anti-HLA-C were the most distantly projected responses in the population with the anti-HLA-B responses to be projected between them. When PCA was applied on the responses against antigens belonging to a single locus, some already known groupings were confirmed while several new cross-reactive patterns of alloreactivity were detected. Anti-HLA-A responses projected through PCA suggested that three cross-reactive groups accounted for about 70% of the variance observed in the population, while anti-HLA-B responses were mainly characterized by a distinction between previously described Bw4 and Bw6 cross-reactive groups followed by several yet undocumented or poorly described ones. Furthermore, anti-HLA-C responses could be explained by two major cross-reactive groups completely overlapping with previously described C1 and C2 allelic groups. A second feature-based analysis of all antigenic specificities, projected as a dendrogram, generated a robust measure of allelic antigenic distances depicting bead-array defined cross reactive groups. Finally, amino acid combinations explaining major population specific cross-reactive groups were described. The interpretation of the results was based on the current knowledge of the antigenic targets of the antibodies as they have been characterized either experimentally or computationally and appear at the HLA epitope registry.

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Section: Discussionmentioning

confidence: 99%

Hidden Patterns of Anti-HLA Class I Alloreactivity Revealed Through Machine Learning

et al. 2021

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“…The current transplant immunology dogma states that the innate immunity is not powerful enough to effectively reject an allograft on its own. However, growing evidence suggests a key role of NK cells in the pathogenesis of immune-mediated graft damage in kidney transplantation [ 76 , 77 , 78 ]. The dominating immune mechanisms associated with graft rejection are mediated by adaptive immune response elements.…”

Section: Sev In Solid Organ Transplantationmentioning

confidence: 99%

Small Extracellular Vesicles in Transplant Rejection

Gołębiewska

Wardowska

Pietrowska

et al. 2021

Cells

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Small extracellular vesicles (sEV), which are released to body fluids (e.g., serum, urine) by all types of human cells, may stimulate or inhibit the innate and adaptive immune response through multiple mechanisms. Exosomes or sEV have on their surface many key receptors of immune response, including major histocompatibility complex (MHC) components, identical to their cellular origin. They also exhibit an ability to carry antigen and target leukocytes either via interaction with cell surface receptors or intracellular delivery of inflammatory mediators, receptors, enzymes, mRNAs, and noncoding RNAs. By the transfer of donor MHC antigens to recipient antigen presenting cells sEV may also contribute to T cell allorecognition and alloresponse. Here, we review the influence of sEV on the development of rejection or tolerance in the setting of solid organ and tissue allotransplantation. We also summarize and discuss potential applications of plasma and urinary sEV as biomarkers in the context of transplantation. We focus on the attempts to use sEV as a noninvasive approach to detecting allograft rejection. Preliminary studies show that both sEV total levels and a set of specific molecules included in their cargo may be an evidence of ongoing allograft rejection.

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“…The disruption of this regulatory process in organ transplants, where HLA Class I mismatches can lead to the absence of inhibitory signals from graft endothelial cells, serves as a danger signal to NK cells. Importantly, the involvement of NK cells in allograft rejection has been noted to occur in different types of solid organ transplants, indicating their involvement with the process of rejection regardless of the organ involved (Benichou et al., 2011; Calabrese et al., 2019; Pontrelli et al., 2020). The importance of MHC Class I inhibition has long been recognized, with the seminal work demonstrating that only tumours with downregulated Class I were killed by NK cells, and not all cancers as was previously believed (Karre et al., 1986).…”

Section: Nk Cell Missing‐self (Ms) In Organ Transplantsmentioning

confidence: 99%

NK cells in antibody‐mediated rejection – Key effector cells in microvascular graft damage

O'Neill

Hidalgo

2021

Int J Immunogenetics

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Antibody‐mediated rejection (ABMR) stands as the major limitation to long‐term transplant outcome. The immunologic understanding of ABMR continues to progress and has identified natural killer (NK) cells as key effector cells promoting and coordinating the immune attack on the graft microvascular endothelium. This review discusses the current concepts outlining the different ways that allow for NK cell recognition of graft endothelial cells which includes antibody‐dependent as well as independent processes.

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The Role of Natural Killer Cells in the Immune Response in Kidney Transplantation

Cited by 43 publications

References 105 publications

Hidden Patterns of Anti-HLA Class I Alloreactivity Revealed Through Machine Learning

Hidden Patterns of Anti-HLA Class I Alloreactivity Revealed Through Machine Learning

Small Extracellular Vesicles in Transplant Rejection

NK cells in antibody‐mediated rejection – Key effector cells in microvascular graft damage

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